Xl. Zhao et al., Effects of the oxadiazine insecticide indoxacarb, DPX-MP062, on neuronal nicotinic acetylcholine receptors in mammalian neurons, NEUROTOXICO, 20(4), 1999, pp. 561-570
The effects of the novel oxadiazine insecticide DPX-MP062 and its metabolit
e (DCJW) on neuronal nicotinic acetylcholine receptors (AChRs) were investi
gated using the whole-cell patch clamp technique in rat embryonic cerebral
cortical neurons in primary culture. DPX-MP062, applied at concentrations o
f 1 and 10 mu M to the bath, reduced the peak amplitude of ACh-induced, rap
idly decaying currents to 46.8 +/- 8.8% (n=9) and 15.7 +/- 5.0% (n=4) of th
e control, respectively. The effect was irreversible after washing with dru
g-free solution. DCJW at either 1 mu M or 10 mu M had similar actions but t
he potency was much less than that of DPX-MP062. The slowly desensitizing c
urrents induced by low concentrations of ACh (0.1-10 mu M) were augmented a
nd those induced by high concentrations of ACh (100-1000 mu M) were inhibit
ed by 10 mu M DPX-MP062 with great acceleration of the current decay in a t
ime-dependent manner. These effects were use independent and reversible aft
er washing with drug-free solution. In contrast, DCJW at 10 mu M did not sh
ow significant effects on peak amplitude and decay phase of the slowly dese
nsitizing ACh-induced current in cortical neurons. These results indicate t
hat the oxadiazine insecticide DPX-MP062 has potent modulating actions on n
euronal nicotinic AChRs. The neuronal nicotinic AChR could be one of the pr
imary target sites of the insecticide in mammals. (C)1999 Intox Press, Inc.